Urolithin a alleviates airway inflammation in acute allergic asthma by suppressing the EGFR/AKT/FOXO3a signaling pathway.

Abstract

Acute allergic asthma represents an acute exacerbation of airway inflammation triggered by allergens, constituting a major clinical challenge that underscores the importance of safe and effective interventions. Urolithin a (UroA), a microbial metabolite of ellagic acid, exhibits prominent anti-inflammatory and antioxidant activities. However, its role and molecular mechanism in acute allergic asthma remain underexplored. In order to systematically elucidate the role of UroA in ameliorating acute allergic asthma and its novel molecular mechanism, an ovalbumin (OVA) -induced acute allergic asthma mouse model and lipopolysaccharides (LPS) stimulated 16HBE cell inflammation model were established in this study. The results showed that UroA (i.g. 20 mg/ [kg (bw)·d]) ameliorated pulmonary pathology and airway inflammation, and suppressed NLRP3 inflammasome activity in both 16HBE cells and lung tissue. Mechanistically, UroA targeted the EGFR-mediated AKT/FOXO3a phosphorylation pathway, thereby blocking NLRP3 inflammasome activation, consistent with the effects of the EGFR inhibitor erlotinib and FOXO3a knockdown. Collectively, these findings identify that regulating NLRP3 inflammasome activity via the EGFR/AKT/FOXO3a pathway is a key mechanism by which UroA alleviates airway inflammation, supporting its potential as a promising candidate for the prevention and treatment of this disease.